ROME — Italian Prime Minister Matteo Renzi resigned on Sunday night after suffering a crushing defeat in a referendum on constitutional reform.

The 41-year-old center-left leader’s attempt to persuade Italians to streamline the lawmaking process and centralize more political power met with a resounding ‘no.’

His opponents won between 58 and 60 percent of votes, according to TV exit polls, while Renzi’s ‘yes’ campaign managed just 40-42 percent. High voter turnout of more than 66 percent made it an even more conclusive defeat for the former mayor of Florence.

“I lost. In Italian politics, no one ever loses,” he told a news conference just past midnight. “But I am different. My political experience in the government comes to an end here.”

“The ‘no’ won in an extraordinarily clear way. Now it’s up to them to come up with concrete proposals and reforms,” Renzi said, adding that he would formally advise President Sergio Mattarella of his decision on Monday, after saying goodbye to his cabinet.

Renzi’s defeat constitutes another populist setback for the European Union, following the U.K.’s Brexit vote in June. Although Austria’s presidential election on Sunday night saw off a challenge from the far-right, the ‘no’ campaign in Italy was led by populists such as Beppe Grillo’s anti-establishment 5Star Movement, the far-right Northern League and ex-premier Silvio Berlusconi.

In a further note of concern for the E.U., the 5Star Movement has previously called for a referendum on Italy’s membership of the eurozone and the renegotiation of the country’s public debt, though opinion polls have suggested Italians would not vote to leave the euro.

As head of state, Mattarella will now be in charge of calling new elections and/or setting up a temporary technocratic government. The Northern League’s Matteo Salvini told POLITICO before Renzi had even stepped down that he was “ready to run for prime minister.”

Renzi’s proposed constitutional reform was also opposed by some within his own Democratic Party (PD), such as former prime minister Massimo D’Alema, and moderate figures such as the former European commissioner and ex-prime minister Mario Monti.

The Renzi camp included European Commission President Jean-Claude Juncker, who said last week that he “would like the ‘No’ not to win.”

Originally published on Politico