The papal city of Avignon remained faithful in the bloody Wars of Religion that had broken out in earnest in 1562, but in the surrounding Venaissin the Huguenots were solidly implanted in Orange and the neighboring Dauphiné, and fierce fighting ensued.
He is remembered for being responsible for the 1545 Massacre of Mérindol, engendered in part by his highly coloured accounts forwarded to Francis I of activities in the Vaudois of Protestants, and encouraged by the papacy to root out the "heretics" in the Venaissin, culminated in the massacre in which hundreds or thousands of Waldensians were killed at the order of the king.