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Cefiderocol is a novel siderophore cephalosporin, which has proven in vitro activity against carbapenem-resistant (CR) Gram-negative pathogens and stability towards all carbapenemases. The aim of this study was to describe the first cases of prescriptions and the efficacy of cefiderocol for compassionate use in the 2 months following its access in France. We performed a national retrospective study of all patients who received at least one dose of cefiderocol from 2 November 2018 to 5 November 2019. We collected clinical characteristics and outcome through a standard questionnaire. Bacterial isolates from 12 patients were centralized and analyzed in the French National Reference Center for Antimicrobial Resistance, and sequenced using Illumina technology. Finally, 13 patients from 7 French university hospitals were included in the study. The main type of infection treated by cefiderocol was respiratory tract infections (RTI, <i>n</i> = 10). The targeted bacteria were <i>Pseudomonas aeruginosa</i> (<i>n</i> = 12), including carbapenemase-producing <i>P. aeruginosa</i> (<i>n</i> = 9), <i>Acinetobacter baumannii</i> (<i>n</i> = 2), <i>Klebsiella pneumoniae</i> (<i>n</i> = 1), and <i>Enterobacter hormaechei</i> (<i>n</i> = 1). Overall, of the 12 patients whose samples were analyzed, 5 <i>P. aeruginosa</i> strains were not susceptible to cefiderocol (4 categorized as resistant and 1 as intermediate) according to Clinical and Laboratory Standards Institute (CLSI) breakpoints. If considering susceptible strains, the cure rate was 6/7, while being 0/5 among not-susceptible strains. This study underlines the necessity to test strains in adequate conditions.