As pope, Felix III was uncompromising and with conviction he defended orthodoxy, in this way wanting to protect the Church from various “wrong” religious doctrines. However, the pontificate of this aristocrat (483-492) from the great Roman Anici family (Anicia) will be remembered most of all as the time of the split between the Eastern and Western Churches which lasted 35 years (until 519 A.D.). The criticism which was put forth by Felix against the Patriarch of Constantinople Acacius, accusing him of supporting the popular in the East monophysitism and putting an anathema on him because of it, as well as warning the Emperor of the Eastern Empire not to get involved in religious affairs, led to the conflict. Acacius ordered the name of Felix to be removed from intercessory prayer. It did not faze the pope much, as he occupied himself with the issue of Catholics in Northern Africa. He supported them in their objections against repeated baptism in the Arian rite, which was forced upon them by the occupying Vandals (followers of Arianism), while strongly condemning those who accepted such baptism. A synod called by him at the Lateran in 487 A.D., excluded them from the community of the Church, while those who repented were given severe long-lasting canonical penalties.

The Bishop of Rome was the son of a clergyman, he had a wife and two children, while his great-grandson was another pope - Gregory I.

After death, his body was laid in the family chapel, next to his wife, in the Basilica of St. Paul Outside the Walls (San Paolo fuori le mura). He is a saint of the Catholic Church.

This pope is either referred to as Felix III or Felix II, depending on the fact, whether the previous pope bearing that name in the middle of the IV century is recognized as a lawful pope or an anti-pope.