Jeremy Corbyn has urged Theresa May's "zombie Government" to make way and declared her "Frankenstein" Brexit deal officially dead as MPs debated a no confidence motion.
His comments come as MPs begin debating the no confidence vote in the Government.
Mr Corbyn said any other Prime Minister would have resigned over the biggest Government defeat in history.
But Theresa May hit back, telling the Commons the Opposition leader has no Brexit plan for the country and refused to say if he would campaign to leave the EU.
Calling again for a general election, Mr Corbyn said: "This Government has failed our country - it cannot govern.
"It cannot command the support of most people and, facing the most important issue at the moment which is Brexit, they failed again and lost the vote last night.
"Isn't it the case, Mr Speaker, that any other Prime Minister faced with the scale of defeat last night would have resigned and this country would be able to choose the Government that they want?
Having criticised the "zombie Government", Mr Corbyn said Mrs May's "Frankenstein deal" was now "officially dead".
He said: "Within two years they have managed to turn a deal from what was supposed to be - I remember this very well - one of the easiest in human history into a national embarrassment."
After Tory Brexiteer and deputy ERG chairman Mark Francois was admonished for "shrieking, yelling, bellowing" across the Chamber, Mr Corbyn continued: "Who has confidence in this government's ability to negotiate a future trade deal with the EU by December 2020 after the shambles we've all witnessed over the past two years?
"This Frankenstein deal is now officially dead and the Prime Minister is trying to blame absolutely everybody else."
In a bid to win support Prime Minister Theresa May will reach out to "senior parliamentarians" across party lines to build a Brexit consensus following the crushing defeat of her plan for leaving the EU.
Conservative MP Andrea Leadsom told ITV News Mrs May is seeking "constructive" and "positive ideas" that will help get her deal through Parliament.
Her comments come amid criticism from Labour around Mrs May's "lack of compromise."
Shadow Chancellor of the Exchequer John McDonnell told ITV News: "The problem that we've got is that for two years Theresa May hasn't even picked up the phone to the other political parties to get them round the table to agree some form of compromise."
The Prime Minister faces a Commons vote of no confidence after seeing her deal with Brussels overwhelmingly rejected by MPs in the House on Tuesday.
While she is expected to survive the latest attack on her premiership, Labour warned she was in danger of scuppering efforts to find a new way forward before they had even started.
Rebel Tory MPs, who helped deliver a massive 230 majority against the Withdrawal Agreement, made clear that they would back the Government in the vote on the no confidence motion tabled by Jeremy Corbyn, as did Mrs May's allies in the DUP.
However MPs from both the Leave and Remain wings of the party warned that she would have to accept major changes to her Brexit plan if she was to stand any chance of winning the backing of Parliament.
Meanwhile, campaigners for a second EU referendum stepped up their efforts, with 71 Labour MPs signing a letter demanding their party commit itself "unequivocally" to a public vote if the no confidence motion fails.
Labour launched a bid to oust the Government after Mrs May's Withdrawal Agreement was overwhelmingly rejected by 432 votes to 202.
Ahead of the vote, Mr Corbyn accused the Prime Minister of preventing the country from choosing its own Government.
He said: "This Government has failed our country - it cannot govern."It cannot command the support of most people and, facing the most important issue at the moment, which is Brexit, they failed again and lost the vote last night.
"Isn't is the case, Mr Speaker, that any other prime minister faced with the scale of defeat last night would have resigned and this country would be able to choose the Government that they want?"
Despite the humiliating defeat, Government sources remained optimistic about seeing off the Labour challenge after the Democratic Unionist Party (DUP) and leading figures from the Brexiteer and Pro-Europe wings of the Tory party said they would back the PM.
With the UK scheduled to exit the EU in just over 10 weeks' time on March 29, the Prime Minister has until next Monday to return to the Commons and present a "Plan B" option.
Speaking ahead of the no confidence on Wednesday Work and Pensions Secretary Amber Rudd said a "Jeremy Corbyn government" would be "devastating" for the country.
The Environment Secretary Michael Gove said he was "confident" the Prime Minister would win the vote in the Commons.
When asked about the next steps for the Government he said: "We need to have a consensus, 17.4 million people voted to leave the European Union, we've got to deliver on that democratic mandate, but we need to do so in a way that commands the support of Parliament and that means talking to people from across the political divide in the national interest."
How the no confidence vote works
Jeremy Corbyn has tabled a motion of no confidence in the Government in an attempt to force a general election.
It is the first time the procedure has been used under the provisions of the Fixed Term Parliaments Act passed by the coalition government under David Cameron.
Mr Corbyn will move the motion tabled in his name as Leader of the Opposition and will speak first in the debate scheduled for Wednesday afternoon.
The Prime Minister will then speak for the Government and at the end of proceedings at 7pm MPs will vote.
If the Government wins there will not be a general election and ministers will carry on in office.
If the Government loses, the Act states there must be an “early” election unless the Government can regain the confidence of the House by winning a confidence vote within 14 days.
During that two-week period there is no statutory limit on how many times a confidence motion can be brought forward and voted on.
In the course of that period the opposition may seek to form alliances within the Commons to demonstrate they are the party most likely to command the confidence of the House and therefore should be given the opportunity to form a government.
ITV News political correspondent Paul Brand points out divides within Labour over Brexit may ironically now be in the spotlight.