Leaving the EU would be an act of "unilateral political disarmament", former Labour Foreign Secretary David Miliband has warned.
In a rare foray into UK politics, Mr Miliband - who quit as an MP in 2013 - said a vote to leave would be disastrous for the UK and the world.
Pro-exit Conservative employment minister Priti Patel said Mr Miliband had always been "wrong" on the EU.
The IMF, meanwhile, has said an UK exit could cause "severe" economic damage.
In its latest assessment of the outlook for the global economy, the International Monetary Fund said an Out vote in the referendum on 23 June on EU membership would disrupt established trading relationships and cause "major challenges" for both the UK and the rest of Europe.
Leave campaigners said the IMF had been "consistently wrong" in its past forecasts for the UK economy.
Mr Miliband quit frontline politics to head the International Rescue Committee aid organisation after narrowly losing out on the Labour leadership in 2010 to his younger brother Ed.
'Born of delusion'
Speaking in a personal capacity at a meeting organised by the Britain Stronger In Europe campaign group, Mr Miliband said: "My message is simple: Now is not the time for unilateral political disarmament.
"No nation in human peacetime history, never mind Britain, has voluntarily given up as much political power as we are being invited to throw away on 23 June."
He added: "For what? A cold, hard lesson in the demon of hubris, born of delusion that the world owes us a break.
"A tragic miscalculation which weakens ourselves, our friends and the international order on which we depend."
He argued that being in the EU boosts British power, security and values and that walking away would diminish its influence and strengthen "our enemies".
"It is said that the world is increasingly divided between firefighters and arsonists. For centuries, Britain has been a firefighter.
"We have always sought to balance great powers and check the abuse of power. There is no shortage of fires that need to be put out around the world at the moment," Mr Miliband said.
"This is no time for Britain to join the ranks of arsonists, and there should be no doubt that Brexit would be an act of arson on the international order."
Speaking on BBC Radio 4's Today before his speech, Mr Miliband said it was "utterly spurious" of Leave campaigners to claim that Britain would regain control of its borders by exiting the EU.
"I think I am right in saying 4,000 EU nationals were turned back at British borders last year. We retain the decision-making power over who comes into Britain...We have got control today over who comes in Britain."
But his comments were criticised by those wanting to leave the EU.
Ms Patel, part of the Vote Leave campaign, said Mr Miliband had been part of a Labour government that "relentlessly surrendered national powers to the EU, gave away billions from the British rebate, campaigned to scrap the pound and failed to retain control over our borders".
"As foreign secretary he signed us up to the Lisbon Treaty that sacrificed important EU vetoes and misled the public about the power of the Charter of Fundamental Rights," she said.
"Voters will be in no mood for lectures from someone who was wrong then on the EU and is wrong now."
Among other EU referendum events on Tuesday, MPs Liam Fox, Alex Salmond and Gisela Stuart, and former foreign secretary Sir Malcolm Rifkind will be giving evidence to the Foreign Affairs Committee on the costs and benefits of EU membership for the UK's role in the world.
Meanwhile, Europe Minister David Lidington will be giving evidence to the EU select committee.