A man has been rushed to hospital with serious head injuries after he was assaulted by a trio of attackers in the city's centre, police say.

Police spokeswoman Julie-Anne Newman said investigators believe the man was attacked by three men on La Trobe Street, near Russell Street, about 9am on Sunday.

He was taken to the Royal Melbourne Hospital with serious head injuries.

Three men have been taken into custody and are assisting police with their enquires.

The assault follows a statewide police blitz on alcohol misuse, violence and anti-social behaviour on Friday and Saturday nights.

Seventy-six people were arrested after police flooded the streets of Melbourne, Yarra, Ballarat and Geelong.

Officers visited more than 500 licensed venues and performed 4935 breath tests.

The crackdown, dubbed Operation Unite, was conducted in jurisdictions across Australia and New Zealand.