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One of the earliest churches built in honor of St. Francis, this bulky structure with three Gothic apses and an octagonal bell tower was raised in the mid-13th century. Inside, all three apses were painted with high-quality frescoes by the Eugubine school. (There's a free light switch behind the speaker next to the confessional on the left aisle to illuminate the chapels.)

The chapel to the right of the main apse was frescoed in the 14th century on two levels with the Life of St. Francis in the upper half and a gaggle of saints in the lower. The main apse has some ceiling-scraping, 13th-century frescoes of Christ Enthroned with Saints, while the chapel to the left contains a deteriorating but well-painted cycle on the Life of the Virgin by Gubbio's early-15th-century master Ottaviano Nelli. Some fine 17th-century altarpieces line the right aisle, and a 16th-century Crucifixion by Benedetto Nelli hides in the sacristy. A cloister behind the apse (enter around the back at Piazza 40 Martiri no. 4) preserves a 14th-century Crucifixion fresco and pieces of a 3rd-century-A.D. Roman floor mosaic that still show some color.