Deputy Prime Minister Dominic Raab has been urged to "grow a backbone" and demand a resignation from Boris Johnson after the PM said he was envisioning staying in the job until the "mid 2030s".
Labour deputy leader Angela Rayner said a "million more people" would be in poverty if Mr Johnson was allowed to remain in his post as desired, and "working people will be paying £500 billion more in tax by 2030".
She told PMQs Britain cannot "stomach" Mr Johnson for another eight years, as she urged him to "call a general election and see where the people are".
She added: "This week the government lost two by-elections in one day, the first in three decades. It's no wonder that the Prime Minister has fled the country and left the honourable member to carry the can.
"The people of Wakefield and Tiverton held their own vote of no-confidence. The prime minister isn't just losing the room, he is losing the country."
The PM was absent from PMQs, instead attending a Nato summit in Madrid where world leaders are discussing how the alliance can protect itself against the growing threat from Russia.
He's been out of the country since Thursday, the day his party lost two by-elections, and will not return until Friday.
On Sunday, speaking from Rwanda, he said: “At the moment I am thinking actively about the third term and you know, what could happen then. But I will review that when I get to it.”
He added that this could stretch into “the mid-2030s”.
Critics say he's been attempting to act as an international statesman to distract from the intense political pressure he's under at home - he lost his party chairman Oliver Dowden over the election defeats and is being attacked by his own backbenchers over the Northern Ireland Protocol Bill.
And a row is brewing within his own party after it was indicated he would be ditching a manifesto pledge to keep defence spending at least 0.5% above inflation.
On Tuesday, a senior government source has acknowledged the inflation rate rising to 11% this year could mean the UK is forced to abandon its pledge.
"The manifesto was written before £400 billion had to be spent locking people up for their own safety because of the global pandemic," a senior government source said.
"There is a reality check on things that were offered in a different age which is the only reasonable thing that we can expect."
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The 2019 Tory manifesto commitment was for the budget to be increased "by at least 0.5% above inflation every year of the new parliament".Defence Secretary Wallace is calling on him to significantly boost defence spending in the years ahead to counter the growing threat from Russia.
He's reportedly written to Prime Minister Johnson calling for a 20% increase in defence spending to meet shortfalls in military capabilities.
Ms Rayner said: "The prime minister is at war with his own defence secretary after confirming he will break his manifesto pledge on increasing defence spending.
"Under this government, Britain is set to have less troops, less planes and less ships. The only thing the prime minister's interested in is defending his own job.
"Just how many more troops have to lose their jobs before he finally says enough is enough?"
Deputy Prime Minister Raab replied: "In fact, a £24 billion increase for the armed forces. Spending on the armed forces is rising to 2.3% of GDP again, making us the largest military spender in Europe."
"Frankly we'll take no lessons from (her) when it comes to security in this country, first thing she did when she became an MP in 2016 voted against Trident, leaving us exposed, and she was campaigning for the right honourable member for Islington North (Jeremy Corbyn) to be prime minister, someone who would take us out of Nato."
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Ms Rayner, who was allowed to take the place of Keir Starmer at PMQs in order to face her opposite number, hit back: "Talking about Nato, where was the honourable member when (during) the situation in Afghanistan? On a sun lounger, that's where. I'll take no lectures from the honourable member when it comes to doing your job."
She added: "When will the deputy prime minister finally grow a backbone and tell the prime minister the game is up?"
At the Nato summit, the PM will tell member nations that the alliance "keeps our people safe every day. But over the next ten years the threats around us are only going to grow".
The PM is urging Nato members to boost investments in the military force to above 2% of their country's GDP.
"We need allies – all allies – to dig deep to restore deterrence and ensure defence in the decade ahead.
"The 2% was always meant to be a floor, not a ceiling and allies must continue to step up in this time of crisis."