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A native of Naples, he was ordained a priest in 1724. He was consecrated by Cardinal d'Alsace and served as titular archbishop of Corinthus from 1725. He was archbishop of Naples from 1734 until 1754. In this capacity, he conducted a search for the relics of Agrippinus, an early bishop of the city. He found a marble vase with the following words written: "Indeterminate relics that are believed to be the body of Saint Agrippinus." He also summoned Stefano Pozzi to decorate the cathedral at Naples.
His clandestine attempt to introduce the Inquisition to Naples in 1746, resulted in a violent popular uprising, whereupon Charles III forced him to renounce his see and leave the capital. He did so with the greatest of reluctance, attempting first to remedy the situation from Rome, but finally resigned the Archbishopric in early 1754.
In 1756, he became prefect of the Congregation for the Evangelization of Peoples. He later became Bishop of Palestrina in 1753, Bishop of Porto e Santa Rufina in 1759, and Bishop of Ostia in 1761. He belonged to the conservative zelanti faction in the College of Cardinals. He became Dean of the Sacred College in June 1761.
Spinelli died at Ostia in 1763.