He fought firmly the spread of Calvinism in Languedoc, supported by the French queen Catherine de' Medici, who had grown up with Lorenzo after her father's death.
He was created cardinal by Pope Paul IV in the consistory of March 15, 1557, with the title of Santa Balbina.
Later he was archbishop of Albi (1561), archbishop of Aix-en-Provence (1568-1571) and archbishop of Siena from 1568.
He died at Avignon in 1571.