Francesco Spera was ordained a priest in the Order of Friars Minor. On 11 May 1587, he was appointed during the papacy of Pope Sixtus V as Titular Archbishop of Nazareth. On 24 May 1587, he was consecrated bishop by Decio Azzolini, Bishop of Cervia, with Francesco Carusi, Bishop of Valva e Sulmona, and Franciscus Panicarola, Titular Bishop of Chrysopolis in Arabia, serving as co-consecrators. He served as Titular Archbishop of Nazareth until his death on 28 Oct 1587.