Fluorescent diamond nanocrystals are attracting increasing interest for a broad range of applications, from biolabeling and single particle tracking to nanoscale magnetic field sensing. Their fluorescence stems from nitrogen-vacancy color centers created within synthetic diamond nanoparticles by high-temperature annealing, which results in the association of pre-existing nitrogen impurities and vacancies generated by high-energy particle (electron, proton, or helium ion) beam irradiation. Up to now, diamond nanocrystals have been irradiated as dry powder in a container or deposited as a thin layer on a flat substrate, depending on the type and energy of the irradiating particles. However, these techniques suffer from intrinsic inhomogeneities: the fluence of particles may vary over the whole sample area, as well as the thickness and density of the nanodiamond layer. Here, we present an approach based on direct large-scale irradiation of nanodiamonds in aqueous colloidal solution by high-energy protons. This approach results in a larger fraction of fluorescent particles, with a more homogenous distribution of nitrogen-vacancy centers per particle and less severe lattice damages compared to dry powder irradiation.