In the adenosine receptor (AR) subfamily of G protein-coupled receptors (GPCRs), biased agonism has been described for the human A1AR, A2BAR and A3AR. While diverse A3AR agonists have been evaluated for receptor binding and Gi-mediated cAMP signalling, the β-arrestin2 (βarr2) pathway has been left largely unexplored. We screened nineteen diverse adenosine derivatives for βarr2 recruitment using a stable hA3AR-NanoBit®-βarr2 HEK293T cell line. Their activity profiles were compared with a cAMP accumulation assay in stable hA3AR CHO cells. Structural features linked to βarr2 activation were further investigated by the evaluation of an additional ten A3AR ligands. The A3AR-selective reference agonist 2-Cl-IB-MECA, which is a full agonist in terms of cAMP inhibition, only showed partial agonist behaviour in βarr2 recruitment. Highly A3AR-selective (N)-methanocarba 5'-uronamide adenosine derivatives displayed higher potency in both cAMP signalling and βarr2 recruitment than reference agonists NECA and 2-Cl-IB-MECA. Their A3AR-preferred conformation tolerates C2-position substitutions, for increased βarr2 efficacy, better than the flexible scaffolds of ribose derivatives. The different amino functionalities in the adenosine scaffold of these derivatives each seem to be important for signalling as well. In conclusion, we have provided insights into ligand features that can help to guide the future therapeutic development of biased A3AR ligands with respect to G-protein and βarr2 signalling.