As private secretary to Pope Urban, among his most valuable services was that of purchasing old works of art, or commissioning new works, for that inveterate collector; among the artists he encouraged was Claude Lorrain. He was rewarded at the end of Urban's pontificate by being raised to the purple as cardinal priest of S. Crisogono on Aug. 31, 1643. He was appointed bishop of Orvieto in 1644.
Throughout his life, he remained very devoted to his home town and region. In addition to beautifying Usigni, he was instrumental in developing iron mines in the area, and he was also so greatly devoted to Rita of Cascia (beatified by Urban in 1627), adorning her church in that town and promoting her cult, that he is often considered to have been the main force in establishing her present cult and popularity. The second edition (1652) of Girolamo de Ghetti's Breve Racconto della Vita e Miracoli della B. Rita da Cascia is dedicated to him.
Poli died in Orvieto in 1653: he was buried according to his wishes in the Chapel of the Guardian Angel in his titular church of San Crisogono.