At first glance, it would seem very difficult to follow a film so thoroughly rooted in the Zeitgeist of a decade and a half ago. But a funny thing has happened: The fashion vanity that Zoolander spoofed went mainstream. Phones in pockets plus the proliferation of social media turned mugging for the camera into ordinary, everyday human behavior. It’s impossible to look at Stiller doing the pouty-serious Blue Steel or Magnum and not think of the bazillion Instagram selfies floating around the Internet. A lot of times, all of us are making the same exact face, without irony.

“That look came out of me in the mirror at home, when I brush my hair or whatever,” Stiller says of Blue Steel. “I guess with the selfie culture, it’s just a natural extension. Did I have any idea that it would live on? No.”

Now that Stiller’s back playing Zoolander, “it’s hard for me to not do it when somebody wants to take a picture with me. I just go into it, like a trained dog.”

He’d talk to me dressed in these absurd outfits, and that hair,” Cruz says of being on set with Stiller. “I couldn’t stop laughing in his face

When Zoolander 2 begins, we find our Derek shamed from fashion, living life as a recluse in the wintry hollows of New Jersey. Lured out of retirement to solve a European murder mystery involving celebrities and selfies—look, did anyone expect le Carré?—Zoolander reunites with Hansel and tangles again with Mugatu. There are turns from Kristen Wiig as a Donatella Versace–like mogul, Benedict Cumberbatch as the new model-of-the-moment, named All, and Justin Bieber does a sublime job as Justin Bieber.

Finally, there’s a seductive new character: Valentina Valencia, a motorcycle-riding Interpol special agent—fashion division—played by the one and only Penélope Cruz.

“I was in South Africa in a supermarket buying diapers, and my phone rang and it was Ben,” Cruz tells me over a late-afternoon drink (OK, I had the drink) at the Mandarin Oriental hotel overlooking Central Park. She is wearing a patterned dress from the Russian designer Ulyana Sergeenko.

“I’m one of those people who’s seen the first Zoolander four or five times,” she says. “I’ve done comedy in Spain, in my own language, but I’ve always said I want to do more comedies in English. I do all these intense dramas, and all my characters are always suffering. For many reasons I need to once in a while do a crazy comedy.” She laughs and leans back into the hotel sofa. “I said to Ben, ‘Count on me.’ ”

Filming took place over three-and-a-half months in early 2015 in Rome. Stiller calls the experience “both awesome and crazy,” recounting a scene in which he sped a tiny Fiat through narrow streets and kept getting interrupted by pedestrians. (“New Yorkers are kind of like that, too, but they take it to another level there.”) Much of the film was made at the city’s famous Cinecittà Studios, and a climactic scene was staged at the Terme di Caracalla, the ancient stone baths where Fellini shot part of La Dolce Vita. “We shot in the tunnels, at night, in these places where they don’t even do tours,” says Cruz, who will be seen again in May in Ma Ma, a personal project that she also produced.