The aim of this study was to realize a French adaptation of the Big Five Inventory-2 (BFI-2), and to further examine the BFI-2's convergent and discriminant validity via a comparison with the NEO-PI-3 and with the syndromes assessed by the Symptom Checklist (SCL-90-R). Bifactor Exploratory Structural Equation Modeling almost fully supported the BFI-2's factor structure and measurement model with five major factors, 15 facets, and an acquiescence method factor. All the scales measuring the major factors showed excellent reliability and almost all the scales measuring facets showed acceptable to excellent reliability and satisfactory metric and scalar invariance across gender. The BFI-2 domains and facets were found to be strongly correlated with the scales of the NEO-PI-3 measuring similar constructs. The BFI-2 Negative Emotionality domain and its facets were positively related to most of the SCL-90-R scales, and Extraversion and its facets related negatively with Interpersonal Sensitivity and Depression. In conclusion, data from the French adaptation confirmed the relevance of the BFI-2 hierarchical factor structure, as well as its scales' reliability and convergent and discriminant validity, which supports and extends the body of knowledge from the original American BFI-2 and its Danish, Dutch, German, Russian, and Slovakian adaptations.