He inherited the duchy of Bomarzo seven years after the death of the father, thank to intercession of cardinal Alessandro Farnese (the future Pope Paul III). He later married Alessandro's relative Giulia Farnese.
His career as condottiero ended in the 1550s, when he was taken prisoner and the Treaty of Cateau-Cambresis ended the French-Spanish Wars in Italy. Orsini then retired to Bomarzo where he surrounded himself with literates and artists, and devoted to an Epicurean style of life, which negated any contact with religion. Here he had the family completed and, starting from 1547, the famous Park, whose enigmatic constructions and sculptures are one of the most suggestive example of late Renaissance art in Italy.
After the death of his wife he dedicated the park to her memory.
Pier Francesco Orsini died in 1583.