He was born at Marseilles, and his father was also a violinist, having studied with Camille Sivori. He began performing at the age of five and made his debut playing the Beethoven violin concerto at 10. Francescatti was a Paganini specialist, and his recording of the Paganini concerto #1 is still regarded as one of the best ever made. Francescatti also made an historic recording of the Beethoven sonatas for violin and piano with Robert Cassadeus. In addition to being a great technique violinist, he also was capable of playing all of the great concerti. His Saint-Saens concerti #3 is also highly regarded, as is his Bruch and Mendelssohn. As a violinist, Francescatti's tone was regarded as full of light and very singing.
In 1927, he went to Paris to teach at the École Normale de Musique and also conducted the Concerts Poulets.
He made his first world tour in 1931 and his American debut with the New York Philharmonic in 1939.
He died in La Ciotat, Provence-Alpes-Côte d'Azur, France at the age of 89.