An extensively drug-resistant Escherichia coli clinical isolate (N1606) belonging to Sequence Type 361 was recovered from the urine of a patient hospitalized in Switzerland. The strain showed resistance to virtually all _-lactams including the latest generation antibiotics cefiderocol and aztreonam–avibactam. Whole genome sequencing revealed that it possessed two carbapenemase encoding genes, namely blaNDM-5 and blaKPC-3, and a series of additional _-lactamase genes, including blaCTX-M-15 and blaSHV-11 encoding extended-spectrum _-lactamases (ESBLs), blaCMY-145 encoding an AmpC-type cephalosporinase, and blaOXA-1 encoding a narrow-spectrum class D ß-lactamase. Most of these resistance genes were located on plasmids (IncFII-FIA, IncX3, IncI, IncFII). That strain exhibited also a four amino-acid insertion in its penicillin-binding protein 3 (PBP3) sequence, namely corresponding to YRIN. Complete genome analysis revealed that this E. coli isolate carried virulence factors (sitA, gad, hra, terC, traT, and cia) and many other non-_-lactam resistance determinants including rmtB, tet(A), dfrA17 (two copies), aadA1, aadA5 (two copies), sul1 (two copies), qacE (two copies), qepA, mdf(A), catA1, erm(B), mph(A), and qnrS1, being susceptible only to tigecycline, colistin and fosfomycin. In conclusion, we described here the phenotypic and genome characteristics of an extensively drug-resistant (XDR) E. coli ST361 being recognized as an emerging clone worldwide.