On completing his work in Antwerp in 1572 Lefevre returned to France where he soon obtained the post of secretary and interpreter to the Duke of Alençon.
It has been conjectured from some words of his in a poem addressed to Marguerite de France that he was a clergyman; and it has been said that Pope Clement VIII wished to make him a cardinal in his last days, but that he declined.
In 1572 appeared in the fifth volume of the Antwerp Polyglot Bible the result of Lefevre's work, entitled Novum Testamentum syriace, cum versione Latin.
In 1572 Lefevre published in Antwerp a short Syriac text which he had found accidentally thrown together with the Eastern Biblical manuscript above mentioned.
This text, furnished with a Latin translation, appeared under the title D. Seven, Alexandrini, quondam patriarche, de Ritibus baptismi et sacre synaxis apud Syros Christianos receptis liber.
Lefevre tells us (Epistola dedicatoria, p. 4 f.) that he published this text to illustrate the agreement of the ancient Eastern Church with the Western in the important matter of sacramental ritual.
Lefevre was not merely a philologist, he also wrote poetry, usually expressing his support for Catholicism - Vauquelin de La Fresnaye described him as a 'poete tout chrestien'.