“The leaders of the No campaign only want protect their privileges and they know that December 4th is the last chance to get back on track,” Renzi said at a gathering in Florence of supporters of the revisions.
The proposed reforms – deemed the most important in Italy since World War II and already approved by parliament – are aimed at increasing political stability in a country which has had 63 governments since 1945.
They would streamline parliament and the electoral system by bringing an end to the existing system whereby each law must be adopted by both chambers in the same terms – a process that can take years.
The “No” camp draws support from across Italy's broad political spectrum and currently enjoys a slight edge in opinion polls.
On Saturday, several dozen “No” supporters clashed with police outside the disused train station in Florence where “Yes” supporters were gathering.
Renzi described the referendum as a “contest between nostalgia and the future, between those who want to change nothing and those who are looking ahead”.
The centre-left prime minister has backtracked on an earlier pledge to resign if voters rejected the proposed constitutional changes.
Still, a defeat would weaken his position significantly, even within his own Democratic Party, where he faces stiff opposition from a leftist minority.
His party foes include former prime minister and “No” champion Massimo D'Alema.
“D'Alema says he could do better (reforms). So why didn't he during his years in power?” Renzi asked to the cheers of his audience.