Rebel Conservative MPs have joined forces with Labour to inflict a fresh blow on Theresa May's government in a Commons Brexit vote.
It means the government will have to come up with fresh plans within three days if Mrs May's EU withdrawal deal is rejected by MPs next week.
It could also open the door to alternatives, such as a referendum.
No 10 said Mrs May's deal was in the national interest but if MPs disagreed, the government would "respond quickly".
The setback for the PM came as MPs started five days of debate on the withdrawal agreement with the EU, and the framework for future relations, ahead of the meaningful vote next Tuesday.
The government was expecting to have 21 days to come up with a "plan B" for Brexit if, as widely expected, Mrs May's deal is voted down.
But MPs backed calls for it to respond within three working Parliamentary days, a deadline likely to fall on Monday 21 January.
The government lost by 11 votes, with 297 MPs siding with them and 308 against.
Former attorney general Dominic Grieve, the Conservative MP who led the rebellion, said he was acting out of a sense of a "deepening crisis" over Brexit.
He told the BBC there had been too much "can-kicking" by the government and if the PM lost next week's vote, she would need to have "serious dialogue" with MPs about alternative options.
He said there was no need for the prime minister to go to Brussels to try and improve the deal.
"I would rather hope that the government has been focusing on alternatives as it has been pretty clear for three to four months that the PM's deal is in trouble," he added.
Fellow rebel Sarah Wollaston said she and other MPs opposed to a no-deal exit were engaged in a "guerrilla campaign" to show that it would never get the consent of Parliament.