C.pomonella is a pest of apple and pear present on all continents, against which one of the most effective non-chemical control method is the use of CpGV, a highly specific virus. Since 2004, cases of resistance to the CpGV-M isolate, the only one used since 1992, have been observed. This problem has been overcome by the use of two alternative viral isolates CpGV-R5 and CpGV-V15 which bypass this resistance in Europe. These are actually mixtures of viral genotypes. In 2020, during a resistance monitoring program conducted on 32 wild populations of C.pomonella from European orchards, we detected for the first time populations with multiple resistance to CpGV-M and CpGV-V15. Moreover, 3 populations show resistance to all three isolates, i.e. all isolates used in France to date. The ratio of resistance of these populations to the CpGV-M isolate is over 300, but only around 10 for the two new isolates. This discovery calls into question this alternative control method, and raises the issue of a very rapid evolution of resistance to a bio-pesticide. The sustainability of biopesticides is therefore questioned.