Rebel Conservative MPs join with Labour as a fresh blow to the government in a Commons Brexit vote.
The government has now got three days to come up with a new plan if Mrs May's EU withdrawal deal is rejected by MPs next week. A second referendum looks likely if Mrs. May fails to get the Parliament to back her.
The government lost by 11 votes, with 297 MPs voting with them and 308 against.
The government was expecting to have 21 days to come up with a "plan B" for Brexit if Mrs May's deal is voted down.
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.