When rumours of the imminent death of Pope Julius II spread, he spurred the Roman population to rebel against the Papal authority; however, when the Pope recovered he was condemned. Colonna was later rehabilitated by Leo X, and created cardinal. He then became famous for his banquets and intellectual activities.
He was a protagonist in the Sack of Rome, when, with a group of mercenaries and peasants from its fiefs in the Lazio, he took part in the sack and assumed control of the city while his personal enemy, pope Clement VII, was a prisoner in Castel Sant'Angelo.
Colonna was also a poet. His most famous work is De laudibus mulierum, written for his relative Vittoria Colonna.